U.S. patent number 6,258,338 [Application Number 09/178,259] was granted by the patent office on 2001-07-10 for hollow or cup-shaped microparticles and methods of use.
This patent grant is currently assigned to Sirtex Medical Limited. Invention is credited to Bruce Nathaniel Gray.
United States Patent |
6,258,338 |
Gray |
July 10, 2001 |
**Please see images for:
( Certificate of Correction ) ** |
Hollow or cup-shaped microparticles and methods of use
Abstract
A particulate material which comprises hollow or cup-shaped
ceramic microspheres having a diameter in the range of from 5 to
200 microns. The material may comprise a beta- or gamma-emitting
radionuclide and be used in selective internal radiation therapy
(SIRT) of various forms of cancer and tumours.
Inventors: |
Gray; Bruce Nathaniel
(Claremont, AU) |
Assignee: |
Sirtex Medical Limited (Western
Australia, AU)
|
Family
ID: |
3740605 |
Appl.
No.: |
09/178,259 |
Filed: |
October 23, 1998 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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676381 |
Sep 23, 1996 |
5885547 |
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Foreign Application Priority Data
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Jan 21, 1994 [AU] |
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54724/94 |
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Current U.S.
Class: |
424/1.29;
424/1.11; 424/9.32; 424/9.1 |
Current CPC
Class: |
A61P
35/00 (20180101); B01J 13/04 (20130101); A61K
51/1241 (20130101); A61K 51/1258 (20130101) |
Current International
Class: |
B01J
13/04 (20060101); A61K 51/12 (20060101); A61K
051/00 (); A61M 036/14 () |
Field of
Search: |
;424/1.11,1.29,1.33,1.37,1.65,9.1,9.32,9.321,9.323,9.36,9.4,9.42,9.5,9.51,400
;128/662.02,660.01,653.1 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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0182131 |
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May 1986 |
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EP |
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0369638 |
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May 1990 |
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EP |
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2073589 |
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Oct 1981 |
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GB |
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WO8602093 |
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Apr 1986 |
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WO |
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WO9314788 |
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Aug 1993 |
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WO |
|
Primary Examiner: Jones; Dameron
Attorney, Agent or Firm: Baker Botts L.L.P.
Parent Case Text
This application is a continuation of Ser. No. 08/676,381 filed
Sep. 23, 1996, now U.S. Pat. No. 5,885,547.
Claims
What is claimed is:
1. A method of radiation therapy of a human or other mammalian
patient, which comprises administering to the patient a radioactive
particulate material comprising hollow or cup-shaped microspheres,
said microspheres comprising a beta-radiation emitting
radionuclide, and having a diameter in the range of from 5 to 200
microns wherein the microspheres consist of yttria or another
yttrium-containing compound as base material and the radionuclide
is yttrium-90.
2. A method according to claim 1, wherein the microspheres have a
diameter in the range of from 20 to 80 microns.
3. A method according to claim 1, wherein the radiation therapy
comprises treatment of cancer or tumours in the patient.
4. A method according to claim 3, wherein the radiation therapy
comprises treatment of primary or secondary cancer of the liver of
the patient.
5. A particulate material comprising hollow or cup-shaped
microspheres having a diameter of from 5 to 200 microns, wherein
the microspheres consist of yttria or another yttrium-containing
compound as base material, produced by a process comprising the
steps of:
(a) forming an aggregate of powdered base material with a suitable
binder;
(b) thermal spraying of the aggregate to melt the base material and
vaporize the binder to form the hollow or cup-shaped
microspheres;
(c) solidifying the molten hollow or cup-shaped microspheres.
6. A particulate material comprising hollow or cup-shaped
microspheres which consist of yttria or another yttrium-containing
compound as base material, said microspheres having a diameter of
from 5 to 200 microns.
7. A radioactive particulate material comprising hollow or
cup-shaped microspheres having a diameter in the range of from 5 to
200 microns and comprising a beta-radiation emitting radionuclide,
wherein the microspheres consist of yttria or another
yttrium-containing compound as base material and the radionuclide
is yttrium-90, produced by a process comprising the steps of:
(a) forming an aggregate of powdered base material with a suitable
binder;
(b) thermal spraying of the aggregate to melt the base material and
vaporize the binder to form the hollow or cup-shaped
microspheres;
(c) solidifying the molten hollow or cup-shaped microspheres.
(d) exposing the solidified hollow or cup-shaped microspheres to a
neutron beam to activate the base material to the beta-radiation
emitting radionuclide.
8. A radioactive particulate material comprising hollow or
cup-shaped microspheres having a diameter in the range of from 5 to
200 microns and comprising a beta-radiation emitting radionuclide,
wherein the microspheres consists of yttria or another
yttrium-containing compound as base material and the radionuclide
is yttrium-90.
Description
FIELD OF THE INVENTION
This invention relates to a particulate material which comprises
small hollow or cup-shaped ceramic particles (hereinafter referred
to as "microspheres"), to a process for the production thereof, and
to methods for the use of this particulate material.
In one particular aspect, this invention relates to hollow or
cup-shaped ceramic microspheres which consist of or comprise a
radioactive material, and to the use of these radioactive
microspheres in the treatment of cancer in humans and other
mammals. In this aspect, the radioactive microspheres are designed
to be administered into the arterial blood supply of the organ to
be treated, whereby they become entrapped in the small blood
vessels of the target organ and irradiate it. An alternate form of
administration is to inject the radioactive microspheres directly
into the tumour to be treated.
The particulate material of the present invention therefore has
utility in the treatment of various forms of cancer and tumours,
but particularly in the treatment of primary and secondary cancer
of the liver and the brain. It is, however, to be understood that
this invention is not limited to microspheres of radioactive
material, and extends to microspheres of other ceramic materials
which are suitable for use in the process described herein.
BACKGROUND OF THE INVENTION
Many previous attempts have been made to locally administer
radioactive materials to patients with cancer as a form of therapy.
In some of these, the radioactive materials have been incorporated
into small particles, seeds, wires and similar related
configurations that can be directly implanted into the cancer.
In other approaches, the radioactive materials have been formulated
into microspheres of regular size for injection into the arterial
blood supply of the target organ. When radioactive particles or
microspheres are administered into the blood supply of the target
organ, the technique has become known as Selective Internal
Radiation Therapy (SIRT). Generally, the main form of application
of SIRT has been its use to treat cancers in the liver.
There are many potential advantages of SIRT over conventional,
external beam radiotherapy. Firstly, the radiation is delivered
preferentially to the cancer within the target organ. Secondly, the
radiation is slowly and continually delivered as the radionuclide
decays. Thirdly, by manipulating the arterial blood supply with
vasoactive substances (such as Angiotensin-2), it is possible to
enhance the percentage of radioactive microspheres that go to the
cancerous part of the organ, as opposed to the healthy normal
tissues. This has the effect of preferentially increasing the
radiation dose to the cancer while maintaining the radiation dose
to the normal tissues at a lower level (Burton, M. A. et al.;
Effect of Angiotensin-2 on blood flow in the transplanted sheep
squamous cell carcinoma. Europ. J. Cancer Clin. Oncol. 1988,
24(8):1373-1376).
When microspheres or other small particles are administered into
the arterial blood supply of a target organ, it is desirable to
have them of a size, shape and density that results in the optimal
homogeneous distribution within the target organ. If the
microspheres or small particles do not distribute evenly, and as a
function of the absolute arterial blood flow, then they may
accumulate in excessive numbers in some areas and cause focal areas
of excessive radiation. It has been shown that microspheres of
approximately 25-50 micron in diameter have the best distribution
characteristics when administered into the arterial circulation of
the liver (Meade, V. et al.; Distribution of different sized
microspheres in experimental hepatic tumours. Europ. J. Cancer
& Clin. Oncol. 1987, 23:23-41).
If the microspheres or small particles do not contain sufficient
ionising radiation, then an excessive number will be required to
deliver the required radiation dose to the target organ. It has
been shown that if large numbers of microspheres are administered
into the arterial supply of the liver, then they accumulate in and
block the small arteries leading to the tumour, rather than
distribute evenly in the capillaries and precapillary arterioles of
the tumour. Therefore, it is desirable to use the minimum number of
microspheres that will provide an even distribution in the vascular
network of the tumour circulation.
Similarly if the microspheres or small particles are too dense or
heavy, then they will not distribute evenly in the target organ and
will accumulate in excessive concentrations in parts of the liver
that do not contain the cancer. It has been shown that solid heavy
microspheres distribute poorly within the parenchyma of the liver
when injected into the arterial supply of the liver. This, in turn,
decreases the effective radiation reaching the cancer in the target
organ, which decreases the ability of the radioactive microspheres
to kill the tumour cells. In contrast, lighter microspheres with a
specific gravity of the order of 2.0 distribute well within the
liver (Burton, M. A. et al.; Selective International Radiation
Therapy; Distribution of radiation in the liver. Europ. J. Cancer
Clin. Oncol. 1989, 25:1487-1491).
For radioactive microspheres to be used successfully for the
treatment of cancer, the radiation emitted from the microspheres
should be of high energy and short range. This ensures that the
energy emitted from the microspheres will be deposited into the
tissues immediately around the microspheres and not into tissues
which are not the target of the radiation treatment. There are many
radionuclides that can be incorporated into microspheres that can
be used for SIRT. Of particular suitability for use in this form of
treatment are the unstable isotopes of yttrium (Y-90) and
phosphorous (P-32), although other isotopes such as iodine can also
be used. Yttrium-90 is the unstable isotope of yttrium-89 which can
be manufactured by placing the stable yttrium-89 in a neutron beam.
The yttrium-90 that is generated decays with a half life of 64
hours, while emitting a high energy pure beta radiation.
If the microspheres contain other radioactive substances that are
not required for the radiation treatment of the target tissue, then
unwanted and deleterious radiation effects may occur. It is
therefore desirable to have microspheres of such a composition that
they only contain the single desired radionuclide. In this
treatment mode, it is desirable to have microspheres that emit high
energy but short penetration beta-radiation which will confine the
radiation effects to the immediate vicinity of the microspheres.
For this purpose, yttrium-90 is the preferred radionuclide,
although other radionuclides such as P-32 are also suitable.
Therefore, the ideal microspheres for use in this treatment mode
will consist only of yttria, have a low density relative to pure
yttria, be in the size range of from 20.gtoreq.80 micron, and be
stable so that no material leaches from the microspheres when
administered into the body of a human or other mammalian
patient.
In the earliest clinical use of yttrium-90-containing microspheres,
the yttrium was incorporated into a polymeric matrix that was
formulated into microspheres. While these microspheres were of an
appropriate density to ensure good distribution characteristics in
the liver, there were several instances in which the yttrium-90
leached from the microspheres and caused inappropriate radiation of
other tissues.
In one attempt to overcome the problem of leaching, a radioactive
microsphere comprising a biologically compatible glass material
containing a beta- or gamma-radiation emitting radioisotope such as
yttrium-90 distributed throughout the glass, has been developed
(International Patent Publication No. WO 86/03124). These
microspheres are solid glass and contain the element yttrium-89
which can be activated to the radionuclide yttrium-90 by placing
the microspheres in a neutron beam. These glass microspheres have
several disadvantages including being of a higher specific gravity
than is desirable, containing other elements such as alumina and
silica which are activated to undesirable radionuclides when placed
in a neutron beam, and requiring large numbers of microspheres in
order to deliver the required amount of radiation to the target
tissue.
There have been several reports of clinical studies on the use of
solid glass radioactive microspheres. In one report, ten patients
with primary hepatocellular carcinoma were treated, however no
patient had a complete or partial response (Shepherd, F. et al.,
Cancer, Nov. 1, 1992, Vol. 70, No. 9, pp 2250-2254).
A further development in order to overcome the problem of leaching,
was the production of light polymeric ion-exchange microspheres
that did not leach their yttrium content when injected into the
body. Using these microspheres, a high objective response rate for
patients with secondary cancer in the liver was obtained when the
microspheres were injected into the hepatic artery (Gray, B. N. et
al.. Regression of liver metastases following treatment with
Yttrium-90 microspheres. Aust. N. Z. J. Surg. 1992, 62:105-110).
One disadvantage of such polymeric ion exchange microspheres is
that the yttrium-90 radionuclide must be added to the microsphere
after neutron activation of the stable isotope of yttrium-89. This
requires the use of specialised facilities and potentially is
hazardous to the manufacturing personnel. Furthermore, the
polymeric microspheres contain only a low percentage of
yttrium.
Using the technique described by Gray et al., other clinical
studies in patients with secondary liver cancer have demonstrated a
very high response rate using low density yttrium-90 containing
microspheres. In one study in patients with metastatic liver
cancer, the majority of patients benefited from treatment with
radioactive microspheres with appropriate physical characteristics,
especially when combined with perfursion of cytotoxic drugs into
the arterial circulation of the liver (Gray, B. N. et al.,
supra).
SUMMARY OF THE INVENTION
In one aspect, the present invention provides a particulate
material comprising hollow or cup-shaped ceramic microspheres
having a diameter in the range of from 5 to 200 microns.
In another aspect, this invention provides a process for the
production of a particulate material as described above which
comprises the steps of (a) forming aggregates of powdered ceramic
base material with a suitable binder, (b) heating the aggregates to
melt the base material and vaporise the binder to form hollow or
cup-shaped microspheres, and (c) solidifying the molten hollow or
cup-shaped microspheres.
Preferably, the process for the production of the particulate
material comprises the steps of (i) grinding or otherwise reducing
the ceramic base material to a fine powder, (ii) combining the base
material with a suitable binder to form a slurry, (iii) spray
drying the slurry in order to form aggregates of the base material
combined with the binder, (iv) thermal spraying the spray dried
aggregates so that the base material is melted and the binder
vaporises resulting in distension of the molten base material so as
to form hollow or cup-shaped microspheres, and (v) solidification
of the molten hollow or cup-shaped microspheres, for example by
collection in a cold medium such as water. The microspheres are
then sorted into batches based on size and density to obtain
microspheres having a diameter in the range of from 5 to 200
microns.
The microspheres may consist of or comprise any suitable ceramic
base material or combination of base materials, including by way of
example, yttria, alumina, zirconia or silica, or combinations
thereof. Suitable combinations include, by way of example, the
biologically compatible glass materials disclosed in International
Patent Publication No. WO 86/03124, the disclosure of which is
incorporated herein by reference. In addition to the oxides
mentioned above, other compounds containing yttrium, aluminium,
zirconium or silica which are suitable for forming the particulate
material of this invention may also be used as the base
material.
In a particularly preferred embodiment of this invention, the
microspheres comprise yttria or another yttrium-containing compound
or salt of yttrium as the base material component thereof. These
preferred microspheres may be rendered radioactive by exposure to a
neutron beam that activates the base material to the material
radionuclide yttrium-90. In addition, these preferred microspheres
do not leach the base material of which they are composed, and are
biologically compatible.
The present invention further extends to a radioactive particulate
material comprising hollow or cup-shaped ceramic microspheres, said
microspheres comprising a beta- or gamma-radiation emitting
radionuclide and having a diameter in the range of from 5 to 200
microns.
Preferably, the beta-radiation emitting radionuclide is
yttrium-90.
The present invention also provides a method for radiation therapy
of human or other mammalian patient, which comprises administration
to the patient of a radioactive particulate material as described
above.
In yet another aspect, this invention also extends to the use of a
radioactive particulate material as described above in radiation
therapy of a human or other mammalian patient.
DETAILED DESCRIPTION OF THE INVENTION
In order to overcome the problem of leaching of radionuclide from
ceramic microspheres, while at the same time maintaining the
microspheres with a low density, the present invention provides
microspheres with improved characteristics arising from the fact
that the microspheres are either hollow or cup-shaped. These
microspheres can be formulated to be of such a size, shape and
density that they have improved distribution characteristics when
administered into the arterial supply of target organs to be
treated. In addition, as they may be composed entirely of yttria,
each microsphere can deliver a higher amount of ionising radiation
than prior art microspheres. This, in turn, means that a lesser
number can be administered to the target organ in order to deliver
the same radiation dose. In another improvement, since the
composition of the microspheres may be of pure yttria, unwanted
ionising radiation emanating from unwanted radionuclides in the
microspheres is thereby avoided. In another improvement, the
microspheres can be neutron activated after manufacture, thereby
improving the manufacture process.
In the following detailed description, reference is made in
particular to the production and use of hollow or cup-shaped yttria
microspheres in accordance with this invention. It is to be
understood, however, that this description is equally applicable to
the production of similar microspheres using other suitable ceramic
base materials as described above.
In the production of hollow or cup-shaped ceramic microspheres in
accordance with this invention, aggregates or agglomerates of
powdered ceramic base material with a suitable binder material are
formed. The purpose of the binder is to provide enough adhesive
quality and strength to stabilise the aggregates, preferably in
substantially spherical form. The maximum particle size of the
aggregates is generally approximately 75 microns, and typically is
in the range of 5 to 50 microns. The particulate size should be as
uniform as possible to achieve best results in subsequent
processing. Preferably, the aggregates are formed by agglomeration
of fine powdered ceramic base material (for example, powder of
approximately 0.1 up to several microns) using the spray drying
technique in which the fine powder is mixed with a suitable binder
and liquid to form a slurry. The slurry is then pumped to an
atomiser where it is broken up into a large number of small
droplets and dried using hot air to produce the resultant
aggregates, generally in substantially spherical form.
The aggregates are then heated to melt the base material,
preferably using the process of thermal or plasma spraying (for
example, using a D.C. plasma jet) in which very high temperatures
of approximately 17000.degree. C. may be attained to ensure
complete melting of the ceramic base material and vaporisation or
volatilisation of the binder material. In plasma spraying the
aggregates are introduced using a carrier gas such as argon into
the plasma torch which uses a high temperature plasma such as
argon, helium, hydrogen, or nitrogen, or mixtures thereof in the
form of a plasma. The ceramic base material becomes molten and is
then accelerated to a high velocity to be subsequently rapidly
solidified, for example by collection in a body of water. During
the plasma spraying, hollow or cup-shaped particles are formed due
to the presence of large gas bubbles trapped within the molten
material.
After solidification, microspheres comprises of or containing
yttrium-containing compounds such as yttria, can then be irradiated
in a neutron beam to result in the formation of the radioactive
isotope yttrium-90 which is suitable for administration to
patients.
During the production process, some microspheres do not form hollow
spheres but take on a cup-shaped configuration. The cup-shaped
particles are of similar size to the hollow microspheres. The
presence of these cup-shaped particles does not significantly alter
the characteristics of the batch of microspheres that are produced,
and mixtures of both hollow and cup-shaped microspheres can be used
for administration to patients. The invention therefore also
includes the production of cup-shaped microspheres of a size
distribution similar to that of hollow microspheres. In addition,
whilst some microspheres may contain only one hollow pore or void,
others may contain more than one such hollow pore or void. Once
again, the presence of more than one pore in these hollow
microspheres does not significantly alter the characteristics of
the microspheres and accordingly the term "hollow microsphere" as
used herein is to be understood as encompassing both microspheres
with a single hollow pore or void, and microspheres with more than
one hollow pore or void.
The thermal spraying technique results in microspheres with a
variable size range. Microspheres of the desired size of from 5 to
200 micron can be sorted by a process of sieving, or using other
well described techniques for sorting of small particles based on
size. Similarly, the microspheres can be sorted into batches of
similar density using conventional techniques for separating
particles on the basis of density.
One example of a suitable binding material which may be used to
bind the powdered base material during the spray drying process is
polyvinyl alcohol. It will be appreciated that other binding
materials can also be used to bind the base material for spray
drying. The amount of binder material which is used may be varied
as desired. Typically, however amounts of binder material of
between 0.5 and 8 wt %, based on the dry weight of the powdered
ceramic base material, may be used.
Preferably, yttria microspheres are produced by first grinding the
yttria base material to a fine powder, for example up to several
microns in diameter, and then spray drying the powder in the form
of a slurry to form aggregates of the base material. The slurry
contains a binding material which allows the formation of
aggregates when fed through a spray drying apparatus. The spray
dried aggregates can then be fed into a thermal jet (e.g. D.C.
plasma jet) which results in the melting of the spray dried
particles. The binding material used in the slurry during the spray
drying process vaporises in the thermal jet during the process of
melting of the yttria and distends the microspheres into the form
of hollow or cup-shaped particles. The particles are then
solidified, preferably by collection in a cold medium such as
water.
In one embodiment of this invention, there is provided a method by
which yttria can be thermally sprayed so as to form hollow or
cup-shaped microspheres with the desired shape and density for use
in the treatment of various forms of cancer and tumours,
particularly in the liver and brain. These microspheres are
composed of pure yttria, with a preferred size range of from 20 to
80 micron in diameter. The hollow or cup-shaped yttria microspheres
are placed in a neutron beam to activate the yttria to the unstable
isotope yttrium-90, and the radioactive microspheres can then be
used in the treatment of cancers and/or tumours as described
above.
The process that controls the formation of hollow or cup-shaped
yttria microspheres is not limited to yttria and has been shown to
also cause the formation of similar microspheres of other ceramic
materials that can be melted and solidified by the process of
thermal spraying, of which alumina, zirconia and silica are some
examples.
Throughout this specification and the claims which follow, unless
the context requires otherwise, the word "comprise", or variations
such as "comprises" or "comprising", will be understood to imply
the inclusion of a stated integer or group of integers but not the
exclusion of any other integer or group of integers.
Further features of the present invention are more fully described
in the following Examples. It is to be understood, however, that
this detailed description is included solely for the purposes of
exemplifying the present invention, and should not be understood in
any way as a restriction on the broad description of the invention
as set out above.
EXAMPLE 1
In one representative experiment to produce microspheres of the
present invention, 99.99% pure yttria was crushed in an attrition
mill using zirconia particles for 11 hours to produce a fine yttria
powder of approximately 1 micron diameter particles. The powder was
dried and combined with polyvinyl alcohol as a binder to form a
slurry. The slurry was fed through a spray drier which was set to
produce dried particles of approximately 30 to 70 micron in
diameter. The spray dried particles of yttria plus binder were
initially sized to 36-53 micron by sieving and then fed into a DC
plasma torch. In this representative production batch, a Plasmadyne
SG-100 torch was used with an arc gas of argon/helium gas flow
using argon as the carrier gas, under the following conditions:
Arc Gas Flow Rate: Argon (L/min) 40 Helium (L/min) 4 Current (Amps)
900 Voltage (Volts) 44.4 Carrier Gas Argon
The above conditions have been determined to be the optimal torch
conditions and yttria powder conditions to produce hollow yttria
microspheres with a size range from 20 to 80 micron. Various other
plasma torch conditions can be used with different current and
voltage rates. The hollow microspheres so formed are then sized and
sorted by density using a combination of sieving and density
separation to produce the size range required for human or other
mammalian use.
The microspheres are placed in a neutron beam to produce the
beta-radiation emitting radionuclide yttrium-90.
EXAMPLE 2
The technique of Selective Internal Radiation Therapy (SIRT) has
been described above. It involves either a laparotomy to expose the
hepatic arterial circulation or the insertion of a catheter into
the hepatic artery via the femoral, brachial or other suitable
artery. This may be followed by the infusion of Angiotensin-2 into
the hepatic artery to redirect arterial blood to flow into the
metastatic tumour component of the liver and away from the normal
parenchyma. This is followed by embolisation of yttrium-90
containing microspheres (produced in accordance with Example 1)
into the arterial circulation so that they become lodged in the
microcirculation of the tumour. Repeated injections of microspheres
are made until the desired radiation level in the normal liver
parenchyma is reached. By way of example, an amount of yttrium-90
activity that will result in an inferred radiation dose to the
normal liver of approximately 80 Gy may be delivered. Because the
radiation from SIRT is delivered as a series of discrete point
sources, the dose of 80 Gy is an average dose with many normal
liver parenchymal cells receiving much less than that dose.
The measurement of tumour response by objective parameters
including reduction in tumour volume and serial estimations of
serum carcino-embryonic antigen (CEA) levels, is an acceptable
index of the ability of the treatment to alter the biological
behaviour of the tumour.
EXAMPLE 3
Yttria (Y.sub.2 O.sub.3) in the form of angular particles, approx.
size range between 5 to 10 microns (Aldrich Chemical. Ltd.), used
as starting material was subjected to wet attrition milling to
reduce the particle size of the powder to >1 micron for
subsequent spray drying. 1 kg of milling media (1 mm diameter
yttria stabilised zirconia spheres obtained from Commercial
Minerals Ltd.) was placed in a 1 l polyethylene container with up
to 100 g of powder. Sufficient ethanol was added to fill the
container to about 4 mm above the powder and milling media. The
powder was milled (approx. 11 hours) until the size of the majority
of the particles was observed to be less than 1 micron (using a
Scanning Electron Microscope (SEM)).
After milling, the milling media was separated from the powder
using a 0.4 mm sieve. Distilled water was used to wash the milling
media from any remaining powder. Vacuum filtration of the powder
was then carried out using a Buchner funnel and Whatman filter
paper No. 542. The powder was again washed with distilled water,
and stored as wet slurry for spray drying.
Polyvinyl alcohol (PVA) was added as a binder at a concentration of
8 wt %, and the slurry spray dried at a slurry concentration of 38
wt % using a Niro Rotary Atomiser, Denmark. The size of the
agglomerates produced by the spray drier could be controlled by the
slurry feed rate and the rotational speed and diameter of the
atomiser wheel. The inlet temperature (290-300.degree. C.) and the
outlet temperature (100.degree. C.) were monitored by
thermocouples.
Prior to plasma spraying, the agglomerates were sieved using a 38
.mu.m sieve to remove the fines while a 100 .mu.m sieve was used to
screen out the coarse particles.
The spray dried powder agglomerates were then plasma sprayed using
a subsonic (atmospheric) D.C., plasma torch (Plasmadyne SG-100, 40
kW, 900 A). The plasma gases were Ar (44 l/min) and He (4 l/min). A
Metco Powder Feed Unit Type 4MP Model 851 was used to feed the
spray dried agglomerates into the plasma torch by using an argon
carrier gas. In most cases the agglomerates were fed into the torch
between 4-6 g/min. The plasma sprayed material was collected by
directing it into distilled water contained in a stainless steel
vessel. The surface of the water was 300 mm away from the torch
head. After spraying, the water was decanted off and the material
dried.
On examination of the surface morphology and internal structure of
the plasma sprayed yttrium material using the scanning electron
microscope (SEM), fully spheriodized Y.sub.2 O.sub.3 particles
having a generally smooth surface morphology were observed.
Internally, pores were observed within most of the plasma sprayed
material. While the distribution and amount of porosity differed,
most Y.sub.2 O.sub.3 particles contained a single spherical
internal pore or void. In order to investigate the relationship
between pore size and particle size, the "as prepared" plasma
sprayed yttria material was sieved into different size ranges and
the density of each size range measured using a pycnometer. The
results are shown in the following Table, and show that the
measured density decreased with an increase in particle size,
indicating that the relative size of the pore within the particle
increased with increasing particle size.
Particle Size Range Measured Density (.mu.m) (kgm.sup.-3) <20
4.74 20-38 4.35 38-45 3.40 45-53 2.77 53-71 2.50
As described in Example 1 above, the plasma sprayed yttria material
may then be placed in a neutron beam in order to produce
beta-emitting radioactive particles.
* * * * *